Homocysteine (Hcy), a sulfur-containing amino acid, is closely associated with neurovascular diseases when present at elevated levels, a condition known as hyperhomocysteinemia (HHcy). This study investigates the neuroprotective effects of hydrogen sulfide (H2S), a gaseous signaling molecule derived from Hcy metabolism, against Hcy-induced neurodegeneration and cerebrovascular dysfunction. Intracerebral administration of Hcy (0.5 mol/L) in male wild-type mice triggered significant oxidative-nitrosative stress, evidenced by increased malondialdehyde (MDA) and nitrite levels, decreased glutathione (GSH), and enhanced acetylcholinesterase activity. These biochemical changes were accompanied by neuroinflammation, as indicated by upregulated expression of pro-inflammatory cytokines TNF-α, IL-1β, and glial fibrillary acidic protein (GFAP), along with increased inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS).IL-22 Proteinsite
Histopathological analysis revealed severe neuronal damage in the cortical and periventricular regions of Hcy-treated mice, including cellular shrinkage, vacuolation, and disorganized hippocampal architecture. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining confirmed increased apoptosis, while Fluoro Jade-C (FJC) staining highlighted extensive neurodegeneration. Furthermore, Hcy treatment disrupted the blood-brain barrier (BBB) integrity through altered expression of tight junction proteins ZO-1 and occludin, reduced tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), and elevated matrix metalloproteinases MMP-2 and MMP-9, leading to extracellular matrix degradation and vascular remodeling.SHH Protein, HumanFormulation
Administration of sodium hydrogen sulfide (NaHS), a donor of H2S, significantly attenuated these pathological changes.PMID:34726659 NaHS treatment restored redox balance by reducing MDA and nitrite levels while increasing GSH concentrations. It also suppressed neuroinflammatory markers, reduced neuronal apoptosis and degeneration, and improved synaptic integrity, as demonstrated by normalized levels of synaptic proteins PSD-95 and SAP-97. Moreover, NaHS preserved BBB structure by upregulating ZO-1 and occludin expression, inhibiting MMP-2 and MMP-9, and restoring TIMP levels. Behavioral assessments using the novel object recognition test confirmed that Hcy impaired memory function, which was effectively reversed by H2S supplementation.
These findings demonstrate that H2S exerts potent neuroprotective and cerebrovascular-stabilizing effects against Hcy-induced toxicity. By counteracting oxidative stress, inflammation, and BBB disruption, H2S represents a promising therapeutic candidate for mitigating neurodegenerative and vascular complications associated with HHcy, offering potential clinical relevance in conditions such as stroke, Alzheimer’s disease, and vascular dementia.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com